The peptide mimicking small extracellular ring domain of CD82 inhibits epithelial-mesenchymal transition by downregulating Wnt pathway and upregulating hippo pathway.

We have previously demonstrated that the peptide mimicking small extracellular ring domain of CD82 (CD82EC1-mP) could inhibit tumor cell motility and metastasis. However, its acting mechanism is not understood. Here, we reported that the cell motility-inhibitory function of CD82EC1-mP was involved in the downregulation of epithelial-mesenchymal transition (EMT). Both vimentin and E-cadherin are EMT makers. We found that CD82EC1-mP could inhibit the expression of vimentin, but promot the expression of E-cadherin, suggesting that CD82EC1-mP suppressed EMT. Hippo/YAP and Wnt/ß-catenin are both key signal pathways that regulate the EMT process. The futher studies showed that CD82EC1-mP couled activate GSK3ß, promote the phosphorylation of ß-catenin, and inhibit the ß-catenin nuclear location. Moreover, CD82EC1-mP couled activate Hipoo kinase cascade, promote the phosphorylation of YAP, and inhibit the YAP nuclear location. These results suggested that CD82EC1-mP inhibited invation and matestasis via inhibiting EMT through downregulating Wnt pathway and upregulating Hippo pathway.

The peptide mimicking small extracellular loop domain of CD82 inhibits tumor cell migration, adhesion and induces apoptosis by inhibiting integrin mediated signaling.

Within the extracellular domains of metastasis suppressor CD82, the large extracellular loop (EC2) has received much of the attention and its structure and function have been studied in detail. However, little attention has been given to the small extracellular loop (EC1 domain). To investigate the function role of EC1 in metastasis suppression of CD82, the peptide mimicking EC1 amino acid sequence (EC1-mP) was synthesized and its effect on cancer cells behavior was examined. Here, we reported that EC1-mP strongly inhibited cancer cell migration in vitro, attnuated the ability of cancer cells adhesion to fibronectin, and induced the apoptosis. Furthermore, the EC1-mP was showed to supprese the expressions of integrins α5 and ß1, as well as decreased the phosphorylation of FAK and expression of ILK in SW620 cells. Taken together, these results demonstrate that this small peptide has the functional role of CD82 intact molecule. This novel finding will improve our understanding of the mechanism by which CD82 inhibits metastasis, and suggested that EC1 mimic peptide may be a promising candidate for developing anti-metastasis drugs.

The peptide mimicking small extracellular ring domain of CD82 inhibits tumor cell migration in vitro and metastasis in vivo.

BACKGROUND: Tetraspanin KAI1/CD82, a tumor metastasis suppressor, has emerged as a promising molecular target for the management of metastatic disease. However, the peptide mimicking small extracellular ring domain (EC1) of CD82 has not been fully investigated for the function of inhibiting cell migration in vitro and tumor metastasis in vivo. METHODS: Different cancer cells were treated with EC1 mimic peptide in order to detect migration and invasion by the healing assay and transwell. Cell aggregation and adhesion assays were used to investigate the function of homotypic cell-cell aggregation and adhesion to tissue culture plates. Then, we established syngeneic and xenograft animal models to assess the metastasis inhibitory effect of EC1 mimic peptide in vivo. RESULTS: In vitro studies, the EC1 mimic peptide had been showed to promote homotypic cell-cell aggregation, suppress cell migration, invasion and adherence in multiple tumor cell types. In vivo metastasis assays, the EC1 mimic peptide could strongly inhibit the pulmonary metastasis of LCC in syngeneic mice model and SW620 and H1299 in xenograft mice model. CONCLUSION: This novel finding will improve our understanding of the mechanism by which CD82 inhibits metastasis, and suggests that EC1 mimic peptide may be a promising candidate for developing anti-metastasis drugs.

COVID-19 Outbreak Caused by Contaminated Packaging of Imported Cold-Chain Products - Liaoning Province, China, July 2020.

What is known about this topic? Few major outbreaks of coronavirus disease 2019 (COVID-19) have occurred in China after major non-pharmaceutical interventions and vaccines have been deployed and implemented. However, sporadic outbreaks that had high possibility to be linked to cold chain products were reported in several cities of China.. What is added by this report? In July 2020, a COVID-19 outbreak occurred in Dalian, China. The investigations of this outbreak strongly suggested that the infection source was from COVID-19 virus-contaminated packaging of frozen seafood during inbound unloading personnel contact. What are the implications for public health practice? Virus contaminated paper surfaces could maintain infectivity for at least 17-24 days at -25 ℃. Exposure to COVID-19 virus-contaminated surfaces is a potential route for introducing the virus to a susceptible population. Countries with no domestic transmission of COVID-19 should consider introducing prevention strategies for both inbound travellers and imported goods. Several measures to prevent the introduction of the virus via cold-chain goods can be implemented.

Screening of NogoA/NTR-related differential genes in rat sciatic nerve injury signal pathway.

AIM: To screen the differential genes in NogoA/NTR-related pathways that associate with sciatic nerve injury. RESULTS: There was no difference in the expression of NogoA, NTR and Ntrk2. Differential genes existed in 11 differential pathways that include NogoA, NTR and Ntrk2. Pathways closely related to sciatic nerve injury are MAPK, endophagocytosis, apoptosis, neurotrophin signaling and inflammatory mediators. NTRK1, FASLG, LDLR ADRB1 and HTR2A in model rats were downregulated compared with control rats, IL1R1, CSF1R, BCL2L1 and HRH1 in model rats were upregulated compared with control rats. CONCLUSION: MAPK, endophagocytic, apoptotic, neurotrophic factor and inflammatory mediators of ductal mediators may be involved in the sciatic nerve injury in rats. The differentially expressed genes in these pathways may play important roles in sciatic nerve injury.

Nosocomial transmission of human granulocytic anaplasmosis in China.

CONTEXT: Human granulocytic anaplasmosis (HGA) is an emerging tick-borne disease in China. A cluster of cases among health care workers and family members following exposure to a patient with fulminant disease consistent with HGA prompted investigation. OBJECTIVE: To investigate the origin and transmission of apparent nosocomial cases of febrile illness in the Anhui Province. DESIGN, SETTING, AND PATIENTS: After exposure to an index patient whose fatal illness was characterized by fever and hemorrhage at a primary care hospital and regional tertiary care hospital's isolation ward, secondary cases with febrile illness who were suspected of being exposed were tested for antibodies against Anaplasma phagocytophilum and by polymerase chain reaction (PCR) and DNA sequencing for A. phagocytophilum DNA. Potential sources of exposure were investigated. MAIN OUTCOME MEASURE: Cases with serological or PCR evidence of HGA were compared with uninfected contacts to define the attack rate, relative risk of illness, and potential risks for exposure during the provision of care to the index patient. RESULTS: In a regional hospital of Anhui Province, China, between November 9 and 17, 2006, a cluster of 9 febrile patients with leukopenia, thrombocytopenia, and elevated serum aminotransferase levels were diagnosed with HGA by PCR for A. phagocytophilum DNA in peripheral blood and by seroconversion to A. phagocytophilum. No patients had tick bites. All 9 patients had contact with the index patient within 12 hours of her death from suspected fatal HGA while she experienced extensive hemorrhage and underwent endotracheal intubation. The attack rate was 32.1% vs 0% (P = .04) among contacts exposed at 50 cm or closer, 45% vs 0% (P = .001) among those exposed for more than 2 hours, 75% vs 0% (P < .001) among those reporting contact with blood secretions, and 87.5% vs 0% (P = .004) among those reporting contact with respiratory secretions from the index patient. CONCLUSION: We report the identification of HGA in China and likely nosocomial transmission of HGA from direct contact with blood or respiratory secretions.

Molecular epidemic survey on co-prevalence of scrub typhus and marine typhus in Yuxi city, Yunnan province of China.

BACKGROUND: Human rickettsioses are worldwide zoonoses and it is not easy to differentiate them from other infectious diseases because of their atypical manifestation. In recent years the number of patients with fever of unknown causes from Hongta District CDC, Yuxi city of Yunnan Province has been increasing significantly in the summer. Diagnosis of scrub typhus was made by local clinicians. In order to ascertain the disease, we undertook a laboratory investigation for such patients from August 18 to 26, 2005. METHODS: Active surveillance was conducted by Hongta District CDC Yuxi city of Yunnan Province from 2002 to 2004 and basic data were obtained from cases confirmed according to clinical definitions. Average incidences and town-level incidences were calculated during the study periods. Blood samples were analyzed by PCR and serological test. Based on the groEL gene sequences a paired general outer primers (Gro-1 and Gro-2) targeting typhus, spotted fever as well as scrub typhus and two paired inner primers (SF1, SR2 and TF1, TR2) for typhus together with spotted fever and scrub typhus, respectively, were designed to perform a multiplex-nested PCR. Serological assay was carried out by indirect immunofluorescence assay with 7 different rickettsial antigens, i.e., R.mossori, R.sibirica, R.conorii, O.tsutsugamushi, B.quintana, B.henselae and Coxilella burnetii phase II Ag. RESULTS: Epidemiological surveillance showed that from 2002 to 2004, the average incidences of the scrub typhus or scrub typhus with murine typhus were 222.1/10(5), 204.3/10(5) and 109.6/10(5), respectively. Of 13 blood samples taken during acute stage of illness, 6 showed the amplified products for scrub typhus and the sequenced products showed 100%, 99%, 99%, 99%, 99%, 99% similarity to O.tsutsugamushi Karp but they shared the same deduced amino acid sequences, which indicated 100% identity with the heat shock protein of the O.tsutsugamushi Karp strain. Five yielded PCR products for murine typhus and their corresponding nucleotide sequences exhibited 100%, 100%, 99%, 99% and 99% similarity to R. mossori Wilmington and the analyses of predicted amino acid sequences indicated 100%, 100%, 98%, 98% and 98% identity with the heat shock protein of R. mossori Wilmington strain. Of the 8 PCR positive patients, 3 showed a co-infection of scrub typhus with murine typhus. All the 13 serum samples from febrile patients were positive against O. tsutsugamushi and 8 of them were positive against R. mossori. All of the 8 paired specimens had four-fold elevation of antibody against O. tsutsugamushi, and seroconversion for typhus was demonstrated in 3 paired serum samples. Another finding in the study was that a high seropositive prevalence (76.9%) of Q fever was detected. CONCLUSION: It's confirmed that co-prevalence of scrub typhus with murine typhus are occurring in Yuxi city of Yunnan province, China. Other rickettsial diseases also need to be investigated in these areas.

Follow-up analysis on the epidemic strains of Orientia tsutsugamushi in the first outbreak of scrub typhus in Henan Province, China.

To obtain knowledge of the genetic characteristics and types of the epidemic strains of Orientia tsutsugamushi in the first outbreak of scrub typhus in Henan Province, genus and type-specific primers were employed to amplify a fragment of the gene of 56 kDa protein. Serotyping demonstrated that, of the 19 patients [15 patients in recovery phase (10-40 days) and 4 of patients in acute phase (1-7 days)], 4 were infected with Gilliam type, 8 with Kato type, 6 with Karp type, and 1 with an unknown type. Successful genotyping was obtained for only 3 patients, indicating that 2 were infected with Karp type and 1 with Taiwan Kato type. Thus the outbreak of scrub typhus in Henan Province was caused by at least two epidemic strains.

Ganglioside GM3 exerts opposite effects on motility via epidermal growth factor receptor and hepatocyte growth factor receptor-mediated migration signaling.

The ganglioside GM3 exerts its different effects via various growth factor receptors. The present study investigated and comparatively analyzed the opposing effects exerted by GM3 on the migration of mouse hepatocellular carcinoma Hepa1­6 cells via epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (HGFR/cMet). The results demonstrated that GM3 inhibited EGF­stimulated motility, but promoted HGF­stimulated motility of the Hepa1­6 cells via phosphatidylinositol 3­kinase/Akt­mediated migration signaling. It is well established that the main cytokines modulating cell proliferation, invasion and metastasis are different in different types of tumor. This difference may, at least in part, explain why GM3 exerted its actions in a tumor­type specific manner.

[Surveillance on Rickettsia in epidemic areas of scrub typhus in Xinyang areas of Henan].

OBJECTIVE: To understand the epidemic status of Rickettsia in Xinyang areas of Henan province. METHODS: Samples including liver, spleen, kidney from mouse and chigger mites from Xinyang areas and serum samples were detected by nested-polymerase chain reaction (PCR) and indirect immunofluorescence assay (IFA). RESULTS: In 62 viscus samples from mice organs, the positive rates were 16.13%, 8.06% and 6.45% for Orientia tsutsugamushi, R. typhii and Spotted fever group rickettsiae respectively. In blood clots samples from mice, the positive rates were 8.06%, 6.45% and 1.61 % for O. tsutsugamushi, R. typhii and Spotted fever group rickettsiae respectively. Three out of 26 mouse serum samples were positive for the predicted fluorexcent intensity O. tsutsugamushi. CONCLUSION: Using nested-PCR and IFA methods, O. tsutsugamushi, R. typhii and Spotted fever group rickettsiae were detected in the captured mice living in Xinyang areas of Henan province. Results showed that there were intensive natural reserviors of Rickettsia in Henan province, suggesting that the risk of outbreak of Rickettsia in these areas was high.